Johns Hopkins researchers Nickolas Papadopoulos, Ken Kinzler and Bert Vogelstein have spent their careers working on ways not just to treat cancer but to detect it before it becomes a threat. The goal: a blood test for the earlier detection of cancer incorporated into routine medical care. Their dream is closer to reality thanks in part to a $2.15 billion acquisition of their company, Thrive Earlier Detection Corp., one year ago by Exact Sciences Corp., a global leader in cancer-detection testing.
The heart of the researchers’ work is the liquid biopsy, a test done on a blood sample to look for signals derived from cancer cells circulating in the blood. In 2011, they invented SafeSeqS, a next-generation gene sequencing technology that simultaneously and individually analyzed millions of DNA molecules to identify mutations in the bloodstream more accurately than other methods.
Two years later, SafeSeqS was incorporated into a pilot study of their liquid biopsy test, which used cervical fluid obtained during routine Pap tests to detect endometrial and ovarian cancer. The “PapGene” test accurately detected all 24 endometrial cancers and nine of 22 ovarian cancers in the study. In 2018, the researchers reported that PapSEEK, the screening test, was nearly 99% specific for cancer and detected 81% of endometrial cancers and 33% of ovarian cancers in a study of 2,000 samples from nearly 1,700 women.
In 2015, Papadopoulos, Kinzler and Vogelstein, with the help of Johns Hopkins Technology Ventures (JHTV), formed a startup, PapGene, to commercialize the test. JHTV has helped the trio over the years with patent protection, licensing strategy, fundraising and negotiations. JHTV also has provided incubator space and services to help them set up their initial, federally certified lab space.
“JHTV has become an invaluable and essential campus resource, and it has been satisfying to watch the university’s innovation enterprise be leveraged by so many other enterprising faculty and students,” says Papadopoulos, a professor of oncology and pathology at the Johns Hopkins University School of Medicine.
PapGene used lab and office space at FastForward, JHTV’s accelerator, and continued work on the test. Meanwhile, Papadopoulos, Kinzler and Vogelstein developed another liquid biopsy test to detect multiple forms of cancer, called CancerSEEK. A study published in 2018 in Science evaluated CancerSEEK in eight cancer types and found it performed with greater than 99% specificity and with sensitivities ranging from 69% to 98% for the detection of five cancer types — ovarian, liver, stomach, pancreas and esophageal — for which there are no screening tests available for average-risk individuals.
Investors and industry officials reached out to JHTV after the paper was published, says Christy Wyskiel, JHTV’s executive director.
“With this type of technology, with such huge potential to save lives, it was really incumbent on JHTV to move quickly and get the smartest investors and executive team in place to move the technology forward,” she says.
CancerSEEK and methods for the detection of cancer were licensed in 2019, and PapGene ultimately became Thrive Earlier Detection Corp., a new company that launched with $110 million in initial funding, the largest initial investment for a Johns Hopkins technology.
In April 2020, Thrive and researchers from Johns Hopkins announced that a multicancer blood test based on CancerSEEK was given to 9,911 women with no evidence or history of cancer. It safely detected 26 undiagnosed cancers, enabling potentially curative treatment in a subset of them. The study, called DETECT-A (Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing) represented the first time a liquid biopsy blood test was used for that purpose. Three months later, Thrive announced another $257 million in funding. Then, in November 2020, Exact Sciences announced it would acquire Thrive for more than $2.15 billion.
“The acquisition of Thrive is a giant leap toward ensuring blood-based, multicancer screening becomes a reality and, eventually, the standard of care,” Kevin Conroy, CEO of Exact Sciences, said in a statement announcing the deal. “We couldn’t be more excited that Exact Sciences will be at the forefront of this incredible opportunity to serve patients. … By combining the expertise of both organizations, we believe we can bring this powerful technology to patients faster.”
Thrive’s trajectory sends an important signal for researchers at Johns Hopkins, Papadopoulos says: The opportunity is available to translate their discoveries through the commercialization process.
“The success of Thrive was about good chemistry between a great scientific team developing a novel test, designing the right clinical study financed by the Marcus Foundation, a great business team around all aspects of the technology, and letting the results speak for themselves,” says Papadopoulos.
Thrive is positioned to have a significant impact on the Baltimore biotech ecosystem, Wyskiel says. Since its founding, Thrive has conducted its research and development in the 1812 Ashland building, part of Johns Hopkins’ innovation hub on its East Baltimore campus. The company now has 60 employees and 35,000 square feet of lab space in Baltimore, both figures double the numbers from the start of 2020.
“We are extremely proud of our Baltimore presence and deep roots at Johns Hopkins,” says Isaac Kinde, a co-founder of Thrive who now leads technology assessment at Exact Sciences. Kinde earned his doctorate in cellular and molecular medicine as well as his medical degree from Johns Hopkins Medicine.
“We feel a great responsibility,” he adds, “to bring the vision of our Hopkins scientific founders and innovations around blood-based cancer screening for multiple types of cancer into the hands of physicians and patients as quickly as possible.”
Papadopoulos, Kinzler and Vogelstein continue to advise Thrive on scientific and clinical matters. Papadopoulos envisions the company’s test one day being part of routine visits to primary care physicians.
“We knew that our work would ultimately benefit patients,” he says. “While it is rare to see external validation so quickly, we are hopeful that this means the test may become standard of care soon, saving countless lives.”
Wyskiel sees in the trio’s work a winning formula for other inventors seeking to have outsized impact on society.
“It all starts with a scientific team that is laser-focused on solving a big problem. From there, it’s about having a clear plan to turn a technology-based solution into a product: What is it that will get sold? Who will buy it? Who will use it? What regulatory hurdles need to get cleared?” she says. “Finally, it’s about having experienced investors who can provide funding but also guidance and access to leadership talent. Put it all together, and the impossible can become a reality.”